The role of cytoplasmic p57 in invasion of hepatocellular carcinoma.

The role of cytoplasmic p57 in invasion of hepatocellular carcinoma.
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细胞质p57在肝细胞癌侵袭中的作用

DOI:
10.1186/s12876-015-0319-x
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发表时间:
2015-08-15
影响因子:
2.4
通讯作者:
Nan K
Nan K
中科院分区:
医学4区
文献类型:
--
作者:
Guo H;Li Y;Tian T;Han L;Ruan Z;Liang X;Wang W;Nan K

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背景我们的前期研究表明p57下调可促进肝癌的生长和侵袭,目的探讨胞浆p57在肝癌侵袭过程中的作用及其调控机制。此外,我们产生了稳定的lep 57敲低肝癌细胞系,探讨细胞质p57介导的调节机制的免疫沉淀,共聚焦免疫荧光显微镜和western blot的细胞核和细胞质extraction.ResultsOur结果表明,胞浆中的p57表达减少包膜浸润和转移患者的标本(P< 0.05)。胞浆p57表达缺失组p-cofilin表达水平明显降低(P< 0.05)。p57和p-cofilin的共表达在晚期(III + IV)肿瘤患者的标本中减少,肿瘤显示包膜浸润和转移性肿瘤。我们进一步观察到,p57下调降低组装p57和LIM结构域激酶1及其激酶活性,随后降低p-cofilin的水平在cytoplasm. ConclusionsCytoplasm p57可能是一个关键的调节器在肝细胞癌的侵袭通过LIM结构域激酶1/p-cofilin途径。
BackgroundOur previous research suggested that p57 downregulation could accelerate the growth and invasion of hepatocellular carcinomain vitroandin vivo.AimTo evaluate the role of cytoplasmic p57 and its regulatory mechanism during hepatocellular carcinoma invasion.MethodsWe examined the subcellular localization of p57 by immunohistochemistry in 45 pairs of cancerous tissues and adjacent non-cancerous tissues. Moreover, we generated stablep57knockdown hepatoma cell lines to investigate the mechanism of cytoplasmic p57-mediated regulation of invasion by immunoprecipitation, confocal immunofluorescence microscopy and western blot of nuclear and cytoplasmic extracts.ResultsOur results showed that cytoplasmic expression of p57 was reduced in specimens from patients with capsular invasion and metastasis (P< 0.05). Moreover, the level of p-cofilin was decreased in the group lacking cytoplasmic p57 expression (P< 0.05). Co-expression of p57 and p-cofilin was reduced in specimens from patients with tumors at later stages (III + IV), tumors showing capsular invasion and metastatic tumors. We further observed that p57 downregulation decreased the assembly of p57 and LIM domain kinase 1 and its kinase activity, subsequently reducing the level of p-cofilin in the cytoplasm.ConclusionsCytoplasmic p57 might be a key regulator in hepatocellular carcinoma invasion via the LIM domain kinase 1/p-cofilin pathway.